Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer treated with immune checkpoint inihibitors.

Abstract

555 Background: Recent clinical trials such as Keynote-045, EV-201 and Javelin bladder100 have provided new therapeutic agents for metastatic urothelial carcinoma (mUC). However, the only tool that can evaluate the therapeutic responses is a radiological criteria, Response Evaluation Criteria in Solid Tumors (RECIST) in mUC. In the clinical practice, biomarkers that can predict the efficacy and prognosis of various agents are essential to treat these patients, and the search for such biomarkers is urgently needed. We reported that Performance status ≥ 1, liver metastasis and elevated serum cytokeratin 19 fragments (sCYFRA) are the prognostic factors for first-line cytotoxic cheomotherapy (CTC) for mUC. In this study we evaluated pretreated clinical biomarkers including sCYFRA that can predict overall survival (OS) in patients with mUC treated with immune-checkpoint inhibitors (ICI). Methods: Thirty four patients with mUC received pembrolizuab (PB) from February 2018 to July 2020 at our institution. We retrospectively collected performance status, metastasis site, blood neutrophil-lymphocyte ratio (NLR), hemoglobin (Hb), and serum levels of lactose dehydrogenase (LD), alkaline phosphatase (ALP), C-reacted protein (CRP), total protein, albumin, corrected calcium (Ca), carbohydrate antigen19-9, sCYFRA before PB was administered. OS rate were analyzed by Kaplan-Meier curves and log-rank test. Multivariate analysis was carried out using the Cox hazards model. Objective Response rate (ORR) was evaluated based on RECIST (version 1.1). Results: Of 34 patients (Pts), with median age of 73(31-86), during the median follow-up period of 25 (7-126) months, 21patients (65%) had died. Median OS was 9.2 months (0.2-33.4), A 1-year OS rate was 33%. ORR was 33% and 9 Pts was SD (27%) and 14 pts (40%) was progressive disease. On univariate analysis, bone metastasis (p=0.028), LD (p=0.003), ALP (p=0.001), Ca (p=0.003) and sCYFRA (p=0.001) were the significant prognostic factor for OS. On multivariate analysis, ALP (HR9.2, 95%CI [2.89-135.9], p=0.002), Ca (HR7.3, (95%CI [2.36-22.49], p=0.001), sCYFRA (HR 5.0, 95%CI [1.63-15.55], p=0.005) were the significant prognostic factor for OS. Based on these 3 factors we divided pts into three groups, good risk (G1,0 factor), intermediate risk (G2, 1 factor) and poor risk (G3, 2-3 factors)3. There was a significant difference between the three groups for OS on K-M curve (G1 vs G2, p=0.001, G2vs G3, p=0.009). Conclusions: sCYFRA, ALP and Ca were the independent prognostic factors for OS in patients with mUC treated with ICI. sCYFRA was the independent prognostic factor for OS in the 1st line CTC and 2nd line ICI and it can be a prognostic factor though those therapies.